Sepsis, a potentially life-threatening condition triggered by an infection or injury, is the result of an overwhelming inflammatory host response to bacterial infection. During sepsis, the body's immune system is dysregulated as it tries to fight an infection, and this can reduce blood supply to vital organs such as the brain, heart and kidneys which can cause multiple organ failure and ultimately death.
It had long been believed that sepsis merely represented an exaggerated, hyperinflammatory response that led to inflammation-induced organ injury, but recent data indicate that substantial heterogeneity exists in septic patients' inflammatory response, with some appearing immuno-stimulated, whereas others appear suppressed. It is clear that multiple pathological mechanisms contribute to sepsis.
The current view of sepsis includes the concept of a Systemic Inflammatory Response Syndrome (SIRS) that has been induced by an infection. Recent data suggests that an appropriate inflammatory response allows elimination of invading microorganisms without causing damage to tissues, organs, or other systems. However, dysregulated inflammation prevents this elimination and allows sepsis to occur by permitting the physiological alterations that manifest as the SIRS. Macrophage activation is thought to play a central role in the initiation and propagation of the systemic inflammatory response.
Inflammatory cells, and monocytes and macrophages in particular, play a central role in the response to invading pathogens and in the pathogenesis of sepsis (Van Amersfoort, E. S. et al. (2003) Clin. Microbiol. Rev. 16(3):379-414). Macrophages in particular have been directly implicated in numerous pathogenic mechanisms that cause organ damage in the septic patient, including for example cardiac infiltration leading to heart disease (Cuenca, J. et al. (2006) Am. J. Pathol. 169(5):1567-1576)
Despite intense efforts, sepsis remains a serious clinical problem despite improvements in critical care management. Despite widespread availability of antibacterial therapies and the development of improved immunotherapies, there remains a need to improve the efficacy of treatment of sepsis.